Our working hypothesis is that the myriad derangements of uremia can only be understood if the molecular nature of uremia is clarified. We are studying a concrete molecular disorder, abnormal transport of small ligands by albumin in uremia. We have partially purified a ligand (or ligands) from uremic fluids, which is either tightly adsorbed or covalently linked to albumin and reduces the binding of other ligands. We shall purify the inhibitor by sequential chromatography and identify its chemical structure. The effects of the inhibitor on albumin binding several model drugs and dansyl amino acids and transport of PAH by kidney slices will be studied. Abnormal micro-forms of albumin may be related to the binding disorder. After purifying albumin from normal and uremic plasma by affinity chromatography, its micro-forms will be analyzed by isoelectric focusing, its free SH content, fluorescence pattern will be determined, and the binding by whole albumin and separate micro-forms will be tested. Finally, whether similar disorders of enzymatic proteins exist in uremia will be studied.